Diagnostic Odyssey: Whole Genome Sequencing (WGS)

November 6, 2024 updated by: Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Ending the Diagnostic Odyssey: Whole Genome Sequencing (WGS) to Identify Genetic Determinants of Previously Undiagnosed Disease in Children

The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology by understanding the potential value of Whole Genome Sequencing (WGS) in establishing genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS and patient and provider experience with genomic medicine.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology, in order to understand the potential value of WGS in establishing a genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS, and patient and provider experience with genomic medicine. Other clinical information of the type collected by treating physicians and stored in electronic medical records will also be collected to aid in the interpretation of laboratory data. Participants will also be asked to consent for future access of the medical record, future research on biospecimens and data generated from genomic sequencing, and for the ability to re-contact.

As part of this effort, Nicklaus Children's Hospital plans to create a large integrated database that contains the DNA sequences of the participants' whole human genomes and additional health information regarding characteristics and health of the persons whose samples have been sequenced. Scientists can then use the database to try to link those traits, diseases, and other conditions to changes in the sequence of the genome. Nicklaus Children's Hospital plans to make the database available to its collaborators, such as RCIGM, pharmaceutical and biotechnology companies, and other academic institutions which will use the database to find better, innovative ways to prevent, diagnose, and treat cancer and other diseases. De-identified data from this study will be shared with the community at-large, including publications and public databases. In addition, participants will be given the option to allow biospecimens (i.e., residual blood, saliva, CSF, etc.) to be included in biorepositories at Nicklaus Children's Hospital and Rady Pediatric Genomics & Systems Medicine Institute (RCIGM).

The study will provide clinical laboratory-confirmed results related to the affected patient's phenotype, including optional incidental findings unless subjects opt-out for these additional results, to allow for these research findings to be used in clinical care. Furthermore, this study will aggregate data regarding standard clinical genetic testing as well as cost measures to not only identify differences in diagnostic rates, diagnostic accuracy, and times to diagnoses, but to determine the cost-effectiveness of this testing and subsequent changes in care management. Clinical utility will be defined as changes in care that follow directly from results of genetic testing (both positive and negative), including standard clinical tests and WGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.

WGS methods continue to improve and pediatric genomic medicine is a very new field of medical practice. This study will also inform investigators regarding best practices, both in terms of traditional medical outcomes and patient-centered outcomes. Consequently, this study will also act as a biorepository for samples and data as the ability to share genomic and phenotypic data amongst researchers is critical to progressing our understanding of the nascent field of pediatric genomic medicine.

Specific Aims:

  1. Use WGS to identify new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders, and metabolic illness.
  2. Evaluate the diagnosis rate of genetic diseases by WGS in previously undiagnosed patients.
  3. Assess the clinical utility of WGS in the care and management of patients.
  4. Examine the health economics and cost-effectiveness of WGS.
  5. Evaluate the provider, patient and family experience with genomic medicine
  6. Collect biological samples and associated clinical data from pediatric patients who may have a genetic disease and their family members (the "Phenome").
  7. Create, analyze and store genomic data from the biological samples. Genomic data will include genomic (gDNA) sequences, RNA sequences, and/or other related 'omic data (including, but not limited to, pharmacogenomics, transcriptomics, and epigenomics). Genomic data from WGS will include single nucleotide variants (SNVs), structural variants such as copy number testing, genomic rearrangements, gene expression , the "whole transcriptome" or more limited DNA sequencing panels of specific genes or of all exons of genes (the "Exome").
  8. Analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
  9. Identify and study novel gene and disease processes.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Children from 0 to 21 years suffering from unknown diagnoses seen at Nicklaus Children's Hospital

Description

Inclusion Criteria:

  • Symptomatic male or female children ages 0-21 who have un unknown medical condition thought to have an underlying genetic cause after parental consent has been obtained.
  • Willingness of referring provider or other qualified medical staff member to participate in this study by facilitating collection of biologic specimens and clinical information.
  • Patient whose medical condition can be reasonably attributed to a possible genetic etiology.
  • Patient have had at least one diagnostic test without a definite diagnosis.

Exclusion Criteria:

  • Unwillingness to consent to research.
  • Affected adults (>21 years of age), unless they are a biological relative of the affected child.
  • Any patient whose medical condition cannot be reasonably attributed to a possible genetic etiology or there is a prior diagnosis that explains the child's clinical presentation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Family-Based
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Genetic Enrollees
Enrollment of patients for whom WGS may be beneficial. Patients who are ill and for whom a genetic diagnosis is suspected but not yet established.
Genetic: Genetic Enrollees
Identification of new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders and metabolic illness. Samples and data will be stored in a pediatric biorepository. A subset of samples will undergo genetic/genomic analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients enrolled per year
Time Frame: Yearly throughout study completion up to 50 years
Total number of enrolled patients who will undergo WGS testing
Yearly throughout study completion up to 50 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnosis Rate of genetic diseases
Time Frame: Throughout study completion up to 50 years
Proportion of diagnosis rate of genetic diseases by WGS in previously undiagnosed patients
Throughout study completion up to 50 years
Clinical Utility
Time Frame: Throughout study completion up to 50 years
Total number of clinical utility of WGS in the case and management of patients
Throughout study completion up to 50 years
Phenome
Time Frame: Throughout study completion up to 50 years
Total number of biological samples and associated clinical data who have a genetic disease and their family members
Throughout study completion up to 50 years
Clinically-confirmed diagnoses
Time Frame: Throughout study completion up to 50 years
Proportion of clinically-confirmed genomic diagnoses and treatment guidance through the use of new research technologies
Throughout study completion up to 50 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Collaborators

Rady Pediatric Genomics & Systems Medicine Institute

Investigators

  • Principal Investigator: Parul Jayakar, MD, Nicklaus Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2018

Primary Completion (Estimated)

March 1, 2070

Study Completion (Estimated)

March 1, 2070

Study Registration Dates

First Submitted

March 2, 2018

First Submitted That Met QC Criteria

March 2, 2018

First Posted (Actual)

March 8, 2018

Study Record Updates

Last Update Posted (Actual)

November 7, 2024

Last Update Submitted That Met QC Criteria

November 6, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • (WGS) Protocol #20172859

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Genetic Disease

Clinical Trials on Genetic Enrollees

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe